The period from adolescence to emerging adulthood is characterized by multiple developmental transitions and peak incidence of sexually transmitted infections (STIs). Hispanic and African-American women are at high risk for HPV-associated and other sexually transmitted diseases, including cervical cancer and Chlamydia. Subsequent to the approval and release of the quadrivalent (Gardasil) HPV vaccine in 2007, we initiated a prospective cohort study of sexually-active, inner-city, minority women (aged 12-19) attending the Mount Sinai Adolescent Health Center (MSAHC), the largest comprehensive adolescent primary care facility in the U.S. We observed higher rates of HPV infection and associated cervical cytological abnormalities post-vaccination among subjects immunized at age 15 or older who took ?12 months (vs. <12 months) to complete the 3-dose vaccine schedule. Furthermore, we found evidence for increased risk of cervical infection with HPV vaccine types and other STIs among subjects with a history of exposure to psycho-social risk indicators reflecting family disadvantage, psychological distress, and history of childhood abuse/neglect. Last year, the FDA approved a new 9-valent HPV vaccine with a reduced dosing schedule for younger adolescents based on evidence from short term bridging studies of primarily Caucasian and low-risk women with limited numbers of sexual partners. This study will assess the real-world effectiveness of the new vaccine in a high-risk minority population. This unique study cohort also provides opportunities to explore new and innovative areas of research relevant to adolescent health in women, especially with respect to other STIs, and the cervicovaginal microbiome. This is of particular relevance since STI rates are high in this population, with a third acquiring Chlamydia. In addition, we observed that certain types of bacteria found in the cervical specimens from women in our study were associated with increased risks of Chlamydia and HPV infection. Furthermore we hypothesize that the impact of chronic stress and risky behaviors leading to STIs and breakthrough HPV infections may be influenced in part by changes in the cervicovaginal microbiome. To address these health disparities in minority young women, we are proposing to expand our existing cohort and recruit an additional 1108 women with prospective follow-up to age 30 to: 1) determine whether there is a reduction in the incidence of cervical, anal and oral HPV infection and incidence of cervical cytological abnormalities among 9-valent versus quadrivalent HPV vaccinees; 2) study the association between cervicovaginal microbiome and risk of HPV and STIs; and 3) assess the complex associations between psycho-social factors including history of childhood abuse/neglect and risk of HPV and STIs. Data obtained from this study will be essential to understanding the long-term impacts of HPV vaccination in high-risk, minority women not studied in the vaccine trials, and will provide the biological underpinnings for future screening practices, as well as estimating the potential impact of the cervicovaginal microbiome and psycho-social factors on risk of HPV and STIs.